Basic Trial Information

Phase

Type

Age

Trial IDs

Phase II

Biomarker/Laboratory analysis, Treatment

18 and over

10-C-0114NCI-2013-01459, 100114, P10628, NCT01130519

Trial Description

Summary

This phase II trial studies how well bevacizumab and erlotinib hydrochloride work in treating patients with hereditary leiomyomatosis and kidney cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Bevacizumab binds to a protein called vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. Erlotinib hydrochloride may stop the growth of tumor cells by blocking a protein called epidermal growth factor receptor (EGFR) that is needed for cell growth. Giving bevacizumab and erlotinib hydrochloride may be an effective treatment for hereditary leiomyomatosis and kidney cancer.

II. To investigate the effect of bevacizumab/erlotinib on circulating endothelial cells and endothelial progenitor cells and to explore the utility of these markers as surrogates of angiogenesis inhibition.

III. To investigate the effect of bevacizumab/erlotinib on potential biomarkers of angiogenesis in plasma such as vascular VEGF and soluble vascular endothelial growth factor receptor 2 (VEGFR2).

VI. To evaluate modulation of hypoxia-inducible factor 1 (HIF), VEGF and EGFR pathways in leiomyomas (in patients with HLRCC) and in renal tumors (when tumors are accessible for biopsy) following therapy.

VII. To assess the effect of therapy on HLRCC associated uterine and skin leiomyomas.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Eligibility Criteria

Inclusion Criteria:

Ability to understand and the willingness to sign a written informed consent document

Negative pregnancy test (within 7 days of enrollment) in women of childbearing potential

At least 4 weeks from completion of major surgery and a healed surgical incision

Recovery from acute toxicity of prior treatment for RCC (to =< grade 1 the active version of Common Terminology Criteria for Adverse Events [CTCAE] or to a level permitted under other sections of inclusion/exclusion criteria)

No more than two prior regimens targeting the VEGF pathway; no prior bevacizumab therapy

Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as >10 mm with spiral computed tomography (CT) scan

Any known hypersensitivity to bevacizumab, erlotinib or other excipients of these drugs

All men and women of childbearing potential must be willing to use effective contraception as determined by the principal investigator (including but not limited to abstinence, hormonal contraceptives [birth control pills, injections, or implants], intrauterine device [IUD], tubal ligation, vasectomy) from the time of enrollment to at least six months following the last dose of drug

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study

Hypertension not controlled by medical therapy (resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg on at least two occasions over a 24 hour period despite optimal medical management)

Patients with known brain metastases unless treated with an appropriate modality with no evidence of progression/recurrence for > 3 months

Prior invasive malignancy of other histology, with the exception of adequately treated basal or squamous cell carcinoma of the skin, or any other malignancy for which the patient has not required treatment for three years

Patient known to be human immunodeficiency virus (HIV)-positive and requiring antiretroviral therapy (due to the risk of potential drug interactions)

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